“Chemotherapy remains a cornerstone for breast cancer management, likely for many years to come — why not use the drugs slightly better, as described in the PANTHER study?” he asked?

Noting that standard dosing of chemotherapy based on body surface area — a formula established in 1916 on 9 patients — results in marked interpatient variation in pharmacokinetics, toxicities, and efficacy, the PANTHER study randomly assigned 2017 patients with node-positive or high-risk node-negative breast cancer in 86 centers in Sweden, Austria, and Germany between February 2007 and September 2011 1:1 to one of two arms.

In the tailored dose-dense arm, patients received 4 cycles of leukocyte nadir-based tailored and dose-dense adjuvant epirubicin 38-120 mg/m2 (starting at 90 mg/m2) and cyclophosphamide 450-1200 mg/m2 (starting at 600 mg/m2) every 2 weeks, followed by 4 cycles of docetaxel 75-100 mg/m2 (starting at 75 mg/m2) every 2 weeks, with a 3-week pause between epirubicin/cyclophosphamide and docetaxel.

In the control arm, they received 3 cycles of standard 5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2 every 3 weeks followed by 3 cycles of docetaxel 100 mg/m2 every 3 weeks.

Total treatment duration was the same in the 2 arms. The primary end point was breast cancer relapse-free survival assessed in the intention to treat population. Secondary end points included event-free survival and overall survival.

No significant interactions were found in predefined subgroups, including patients with hormone receptor-positive disease or those treated with trastuzumab.

Grade 3/4 hematologic toxicity was higher in the tailored dose-dense arm compared with the control arm, 93% vs 21%. Five cases of myelodysplastic syndrome/acute myeloid leukemia were reported, 3 in the TDD arm and 2 in the control arm.